Unsteady Gait Research Articles

Efficacy and Toxicity of Vincristine and CYP3A5 Genetic Polymorphism in Rhabdomyosarcoma Pediatric Egyptian Patients.

Rhabdomyosarcoma (RMS) is a rare cancer that develops in soft tissue, particularly skeletal muscle tissue and occasionally hollow organs like the bladder or uterus. Vincristine (VCR) is the main therapy used in treatment of RMS, it is an alkaloid produced from vinca and it is one of the most commonly prescribed drugs in pediatric oncology for the treatment of a number of tumors. The CYP3A5 enzyme is responsible for vincristine metabolism. The effect of CYP3A5 genetic polymorphism on the efficacy and toxicity of VCR on RMS patients still needs further research. Genotyping for CYP3A5 SNPs rs776746, rs10264272 and rs41303343 was performed using Taqman Real-Time PCR assays in a retrospective cohort study of 150 RMS pediatric patients treated with vincristine. The relationship between these genotypes and RMS survival was then examined. We found that patients with CYP3A5*3/*3 had the highest incidence of vincristine-induced neuropathy reaching 61.3%. Patients with CYP3A5*1/*3, CYP3A5*3/*6 and the normal metabolizers with CYP3A5*1/*1 had frequencies of 22%, 10.7%, and 4.7%. patients with the lowest frequency of 1.3% were those with the CYP3A5*1/*6 genotype. There was no correlation between the genotypes of CYP3A5*3, CYP3A5*6, CYP3A5*7, and RMS survival. Initial risk, metastasis, response, convulsions, unsteady gait and hepatotoxicity grade had a significant effect on overall survival with p<0.05. CYP3A5*1/*1 have less severe vincristine-induced neuropathy than CYP3A5 *1/*3, CYP3A5 *1/*6 and CYP3A5 *3/*3, CYP3A5 *3/*6. There is a significant influence of CYP3A5 mutation on neuropathy grade and assist of ADL as a part of neurotoxicity.

Accelerated neuropathy among chronic kidney disease patients undergoing hemodialysis: Analysis of an institutional cluster.

Accelerated neuropathy is a rare syndrome of rapidly worsening peripheral neuropathy, typically described in end-stage kidney disease (ESKD) patients undergoing dialysis. In our center, we encountered a surge in the occurrence of accelerated neuropathy among ESKD patients undergoing hemodialysis, which prompted systematic research. In this case-control study, we present the clinical features, electrophysiologic findings, and outcome of a series of patients who developed accelerated neuropathy after commencing hemodialysis for ESKD. Those who initiated hemodialysis and did not develop accelerated neuropathy were included as controls. We used logistic regression to identify predictors of accelerated neuropathy. Among 436 ESKD patients who initiated hemodialysis over 4 years, 17 were diagnosed with accelerated neuropathy. The median-time (interquartile range) from hemodialysis initiation to presentation with accelerated neuropathy was 3 weeks (2-6). It typically presented as acute onset of unsteadiness of gait necessitating assistance for ambulation. Electrophysiology revealed length-dependent symmetric sensorimotor axonal neuropathy. Diabetes mellitus (odds ratio [OR] 4.1, 95% CI 1.2-13.9, p = 0.02), pre-existing peripheral neuropathy (OR 9.25, 95% CI 2.79-30.6, p < 0.001), and serum alkaline phosphatase (OR 1.2 for every 10 U increase, 95% CI 1.00-1.52, p = 0.04) significantly predicted accelerated neuropathy. With continued dialysis and supportive care, neurologic status improved, total-neuropathy score (summary score of peripheral nerve dysfunction incorporating clinical and electrophysiological parameters) declined from 26.5 to 18.4 (p < 0.001) and most regained unassisted ambulation. This study presents the largest series of patients with accelerated neuropathy and has identified predictors. However, in view of the unusually high incidence of accelerated neuropathy we speculate that other unidentified factor(s) could be underlying its pathogenesis.

Late Onset of Severe Demyelinating Peripheral Neuropathy in a 62-Year-Old African American Woman.

Hereditary neuropathies are typically associated with an early onset of symptoms, but same types of neuropathies may also manifest late, after the age 50 years. A 62-year-old African American woman presented with a 6-year history of gait unsteadiness and has been using a walker since the age 57 years after an unwitnessed fall. Gradual worsening of walking difficulties was later followed by decreased dexterity. The family history was negative for neuromuscular disorders, including neuropathy. On examination, the patient had both distal and proximal weakness with distal sensory loss to all modalities and hyporeflexia. Charcot Marie Tooth Examination Score was 12. Previous electrodiagnostic testing at the age 60 years showed severe sensorimotor demyelinating polyneuropathy with bilateral severe carpal tunnel syndrome. Genetic testing showed a homozygous pathogenic mutation in SH3TC2 gene (c.2860C>T; p.Arg954*), associated with CMT4C. CMT4C is the most common recessive demyelinating sensorimotor polyneuropathy and overall comprises 0.4%-1.7% of all patients with Charcot-Marie-Tooth disease. It is more common in French Canadians and Spanish Roma and in recent natural history study; only 1 of 56 patients was African American. This report demonstrates sporadic occurrence of CMT4C in other ethnic groups as well.

Demyelination and Na+ Channel Redistribution Underlie Auditory and Vestibular Dysfunction in PMP22-Null Mice.

Altered expression of peripheral myelin protein 22 (PMP22) results in demyelinating peripheral neuropathy. PMP22 exhibits a highly restricted tissue distribution with marked expression in the myelinating Schwann cells of peripheral nerves. Auditory and vestibular Schwann cells and the afferent neurons also express PMP22, suggesting a unique role in hearing and balancing. Indeed, neuropathic patients diagnosed with PMP22-linked hereditary neuropathies often present with auditory and balance deficits, an understudied clinical complication. To investigate the mechanism by which abnormal expression of PMP22 may cause auditory and vestibular deficits, we studied gene-targeted PMP22-null mice. PMP22-null mice exhibit an unsteady gait, have difficulty maintaining balance, and live for only ∼3-5 weeks relative to unaffected littermates. Histological analysis of the inner ear revealed reduced auditory and vestibular afferent nerve myelination and profound Na+ channel redistribution without PMP22. Yet, Na+ current density was unaltered, in stark contrast to increased K+ current density. Atypical postsynaptic densities and a range of neuronal abnormalities in the organ of Corti were also identified. Analyses of auditory brainstem responses (ABRs) and vestibular sensory-evoked potential (VsEP) revealed that PMP22-null mice had auditory and vestibular hypofunction. These results demonstrate that PMP22 is required for hearing and balance, and the protein is indispensable for the formation and maintenance of myelin in the peripheral arm of the eighth nerve. Our findings indicate that myelin abnormalities and altered signal propagation in the peripheral arm of the auditory nerve are likely causes of auditory deficits in patients with PMP22-linked neuropathies.

Metronidazole: A culprit to balance and speech

In a country like India, oral metronidazole is the commonly prescribed drug of choice for entities such as amebiasis and visceral abscesses. Oral such cases, it is usually well tolerated and safe but can cause serious neurological adverse events. Peripheral neuropathy commonly encounters in practice but central nervous system toxicity is also well documented as it crosses the blood–brain barrier easily. Neurological toxicity of metronidazole may be due to prolonged administration, high doses, or high cumulative doses. Magnetic resonance imaging (MRI) of brain is the modality of choice to evaluate brain involvement. In the brain, the splenium of the corpus callosum, dentate nucleus of the cerebellum, and posterior pons involvement are commonly seen and diagnostic. Here, we have an interesting case report of a patient who was on oral metronidazole treatment for his large liver abscess, presenting with a complaint of neurological symptoms of unsteady gait, vertigo, dysdiadochokinesia, and difficulty in speech. Moreover, thus suspected as metronidazole drug toxicity and further investigated for the same, and MRI typically shows cerebellar and posterior corpus callosal involvement.

Investigation of the Effects of Age-Related Changes in the Vestibular System on Balance: A Review

The vestibular system (VS) undertakes vital tasks for the survival of the individual by perceiving the movement of the head according to gravity and adjusting on balance, autonomic function, spatial perception, and orientation. In addition to being the first system to develop in the intrauterine period, the VS continues to develop with childhood. Although the onset time varies depending on various factors, it is known that VS degenerates with aging. It has also been shown in the literature that the number of sensory vestibular hair cells decreases by approximately 6% per decade from birth to old age. In addition, neurons in the vestibular nuclei are known to decrease by about 3% per decade between the ages of 40 and 90. These age-related changes in VS may cause dizziness, loss of balance, unsteady gait, increased falls and even agitation, loneliness, and loss of self-confidence in elderly individuals. In addition, it is reported in the literature that falls due to vestibular disorder are among the third to tenth leading causes of death among older adults. In this sense, it is very important to determine age-related VS dysfunctions in the healthy aging action plans of the health systems of the countries and in the development of strategies to prevent age-related falls. At the same time, it is very valuable for physiotherapists working in the field of geriatric rehabilitation to know well the age-related changes of VS and its effects on balance in the creation of possible vestibular rehabilitation programs. We think that virtual reality applications applied in addition to vestibular rehabilitation for vestibular disorders are promising, especially hearing problems in the elderly population should not be overlooked and hearing aids should be prescribed if needed.

Activity Detection in Indoor Environments Using Multiple 2D Lidars.

In health monitoring systems for the elderly, a crucial aspect is unobtrusively and continuously monitoring their activities to detect potentially hazardous incidents such as sudden falls as soon as they occur. However, the effectiveness of current non-contact sensor-based activity detection systems is limited by obstacles present in the environment. To overcome this limitation, a straightforward yet highly efficient approach involves utilizing multiple sensors that collaborate seamlessly. This paper proposes a method that leverages 2D Light Detection and Ranging (Lidar) technology for activity detection. Multiple 2D Lidars are positioned in an indoor environment with varying obstacles such as furniture, working cohesively to create a comprehensive representation of ongoing activities. The data from these Lidars is concatenated and transformed into a more interpretable format, resembling images. A convolutional Long Short-Term Memory (LSTM) Neural Network is then used to process these generated images to classify the activities. The proposed approach achieves high accuracy in three tasks: activity detection, fall detection, and unsteady gait detection. Specifically, it attains accuracies of 96.10%, 99.13%, and 93.13% for these tasks, respectively. This demonstrates the efficacy and promise of the method in effectively monitoring and identifying potentially hazardous events for the elderly through 2D Lidars, which are non-intrusive sensing technology.

The Impact of Different Self-Selected Walking Speeds on Muscle Synergies in Transfemoral Amputees during Transient-State Gait

Facing above-knee amputation poses a significant hurdle due to its profound impact on walking ability. To overcome this challenge, a complex adaptation strategy is necessary at the neuromuscular level to facilitate safe movement with a prosthesis. Prior research conducted on lower-limb amputees has shown a comparable amount of intricacy exhibited by the neurological system, regardless of the level of amputation and state of walking. This research investigated the differences in muscle synergies among individuals with unilateral transfemoral amputations during walking at three different speeds of transient-state gait. Surface electromyography was recorded from eleven male transfemoral amputees’ intact limbs (TFA), and the concatenated non-negative matrix factorization technique was used to identify muscle synergy components, synergy vectors (S), and activation coefficient profiles (C). Results showed varying levels of correlation across paired-speed comparisons in TFA, categorized as poor (S1), moderate (S3 and S4), and strong (S2). Statistically significant differences were observed in all activation coefficients except C3, particularly during the stance phase. This study can assist therapists in understanding muscle coordination in TFA during unsteady gait, contributing to rehabilitation programs for balance and mobility improvement, and designing myoelectric prosthetic systems to enhance their responsiveness to trips or falls.

A Retrospective Review of 18 Patients With Childhood-Onset Hereditary Spastic Paraplegia, Nine With Novel Variants

BackgroundHereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative disorders. Our objective was to determine the clinical and molecular characteristics of patients with genetically confirmed childhood-onset HSPs and to expand the genetic spectrum for some rare subtypes of HSP. MethodsWe reviewed the charts of subjects with genetically confirmed childhood-onset HSP. The age at the disease onset was defined as the point at which the delayed motor milestones were observed. Delayed motor milestones were defined as being unable to hold the head up by four months, sitting unassisted by nine months, and walking independently by 17 months. If there were no delayed motor milestones, age at disease onset was determined by leg stiffness, frequent falls, or unsteady gait. Genetic testing was performed based on delayed motor milestones, progressive leg spasticity, and gait difficulty. The variant classification was determined based on the American College of Medical Genetics standard guidelines for variant interpretation. Variants of uncertain significance (VUS) were considered disease-associated when clinical findings were consistent with the previously described disease phenotypes for pathogenic variants. In addition, in the absence of another pathogenic, likely pathogenic, or VUS variant that could explain the phenotype of our cases, we concluded that the disease is associated with VUS in the HSP-causing gene. Segregation analysis was also performed on the parents of some patients to demonstrate the inheritance model. ResultsThere were a total of 18 patients from 17 families. The median age of symptom onset was 18 months (2 to 84 months). The mean delay between symptom onset and genetic diagnosis was 5.8 years (5 months to 17 years). All patients had gait difficulty caused by progressive leg spasticity and weakness. Independent walking was not achieved at 17 months for 67% of patients (n = 12). In our cohort, there were two subjects each with SPG11, SPG46, and SPG 50 followed by single subject each with SPG3A, SPG4, SPG7, SPG8, SPG30, SPG35, SPG43, SPG44, SPG57, SPG62, infantile-onset ascending spastic paralysis (IAHSP), and spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). Eight novel variants in nine patients were described. Two affected siblings had a novel variant in the GBA2 gene (SPG46), and one subject each had a novel variant in WASHC5 (SPG8), SPG11 (SPG11), KIF1A (SPG30), GJC2 (SPG44), ERLIN1 (SPG62), ALS2 (IAHSP), and HACE1 (SPPRS). Among the novel variants, the variant in the SPG11 was pathogenic and the variants in the KIF1A, GJC2, and HACE1 were likely pathogenic. The variants in the GBA2, ALS2, ERLIN1, and WASHC5 were classified as VUS. ConclusionsThere was a significant delay between symptom onset and genetic diagnosis of HSP. An early diagnosis may be possible by examining patients with delayed motor milestones, progressive spasticity, gait difficulties, and neuromuscular weakness in the context of HSP. Eight novel variants in nine patients were described, clinically similar to the previously described disease phenotype associated with pathogenic variants. This study contributes to expanding the genetic spectrum of some rare subtypes of HSP.

Gastric cancer of unusual presentation, the importance of differential diagnosis.

We present the case of a 67-year-old male smoker with no medical history of interest. Admitted to Neurology for frontal headache, unsteady gait, temporospatial disorientation and vomiting. Laboratory tests (including vitamin B12, folic acid, lues) and cranial CT scan were normal, encephalogram compatible with diffuse encephalopathy and lumbar puncture with a finding of leptomeningeal carcinomatosis. In light of these findings, it was decided to look for occult tumor by thoracoabdominal-pelvic CT, which was negative for malignancy. In view of the results of the previous tests, it was decided to perform an endoscopic study. Colonoscopy reveals six 0-IIa Paris polyps in the left colon measuring 7-10 cm, which are removed. Gastroduodenoscopy shows a poorly distensible stomach, with erythematous gastric body mucosa and hard on biopsy. In addition, in the duodenum, three raised lesions with an excavated center (Fig. 1) of about 5 mm were identified and biopsied. Histology findings report mucosal and submucosal infiltration by poorly differentiated carcinoma. Immunohistochemistry positive for CK19, Glipican-3, weak positivity for CK7, conserved expression of MUC5AC and SMAD, negative for SF-1, inhibin, synaptophysin, INSM1, chromogramin, Gata-3 and S-100. The findings were suggestive of infiltration by poorly differentiated carcinoma of probable gastric origin. Unfortunately, during hospital admission the patient presented a progressive clinical deterioration and died two weeks later.

Edouard Manet's portrait of Jeanne Duval: Did Manet portray the disease of which he died?

In 1862, the French artist Edouard Manet painted a portrait of Jeanne Duval, then age 42, who was suffering from a paralyzed leg. Manet depicts her stiffly reclined on a sofa with her foot seemingly disjointed from her body. Duval later became blind. Around 1875, Manet himself began to develop leg pains and an unsteady gait, which progressed in severity until he died of complications of his disorder, during 1883, at age 51. This contribution reviews the clinical information available concerning the neurologic disorders of both the subject and artist and the differential diagnosis for each case, with a focus on whether neurosyphilis may have accounted for their respective illnesses. This contribution also pays tribute to Irwin M. Braverman, MD, who is being honored in this special issue of Clinics in Dermatology for his many contributions to dermatology and for demonstrating how the study of art can be a valuable teaching tool to improve the observational skills of medical students.A Special Message from the Author to Irwin M. Braverman, MD

Study on SH-SY5Y autophagy inhibition and apoptosis induced by methanol extract of Zanthoxylum armatum DC. based on mTOR signal pathway

Abstract Background Zanthoxylum armatum DC. (ZADC) is a novel food raw material resource, offering both edible and medicinal properties. Recent research has unveiled the toxic nature of ZADC, particularly its close association with the nervous system. In a prior study, we observed that administering methanol extract of Zanthoxylum armatum DC. (MZADC) to rats via gavage at a dose of 1.038 g/kg resulted in various neurotoxicity symptoms, including excessive salivation, reduced mobility, unsteady gait, muscle twitching, and altered respiratory rates. Materials and methods We conducted cell-based research to assess the safety of ZADC and elucidate its potential toxic mechanism. In addition, we used experimental methods such as Cell Counting Kit-8, Western blot, and Flow cytometry to detect cytotoxicity in SH-SY5Y cells after intervention with MZADC. Results Following exposure of SY-SY5Y cells with MZADC, a substantial decline in cell viability was observed, accompanied by a concentration-dependent increase in intracellular reactive oxygen species (ROS) levels. Additionally, MZADC induced cellular oxidative stress, leading to elevated malonic dialdehyde (MDA) and superoxide dismutase (SOD) concentrations while decreasing glutathione (GSH) levels. Furthermore, MZADC induced apoptosis at varying doses (20, 40, and 60 μg/mL), and this effect was associated with increased Caspase-3, Bax expressions, and reduced Bcl2 and Bcl2/Bax expressions. In addition, the investigation revealed that MZADC induced autophagy inhibition in SH-SY5Y cells by activating the mTOR signaling pathway, resulting in a decrease in LC3II/LCI and Beclin-1, while increasing p-mTOR/mTOR, p62. Conclusion Consequently, this study suggests that MZADC triggers the mTOR pathway through oxidative stress in SH-SY5Y cells, ultimately leading to apoptosis. Understanding the toxicity mechanisms associated with ZADC can offer a valuable theoretical and experimental basis for its development and utilization.

Movement Disorders in Brain Sagging Syndrome Due To Spontaneous Intracranial Hypotension: A Review.

Spontaneous intracranial hypotension (SIH), a treatable condition that stems from spinal leakage of cerebrospinal fluid, usually presents with orthostatic headache, nausea, vomiting, dizziness, and tinnitus. A subset of patients, especially those with sagging of brain structures ("brain sagging syndrome"), develop several movement abnormalities. As SIH is treatable with epidural blood patch (EBP), movement disorders neurologists should be familiar with this syndrome. The authors performed a literature search in PubMed in July 2024 using the Boolean phrase- (("Brain sagging")OR("Intracranial hypotension"))AND(((((((((("Movement disorders")OR("Involuntary movements"))OR("Tremor"))OR("Dystonia"))OR("Chorea"))OR("Ballismus"))OR("Myorhythmia"))OR ("Tic"))OR("Ataxia"))OR("Parkinsonism")). We tabulated 21 case reports/series that highlighted the presence of movement disorders. The most reported phenomenology is gait unsteadiness. While it usually emerges in the background of the classic SIH symptoms, rarely, patients may present with isolated gait dysfunction. Tremor is the second most reported phenomenology with postural and kinetic tremor being the common subtypes. Holmes tremor has also been reported in SIH. Other reported phenomenologies are parkinsonism, chorea, and dystonia. One study reported a unique phenomenology i.e. compulsive repetitive flexion and breath holding in 35.3% of the patients. In majority of the patients, EBP resulted in substantial clinical and radiological improvement. Brain sagging syndrome due to SIH may present with a wide range of movement disorders. Mechanical distortion of the posterior fossa and subcortical structures result in the emergence of such movement abnormality. SIH adds to the list of conditions that result in "treatable movement disorders." Therefore, movement disorders neurologists should be versed with the diagnosis and clinical features of this condition.

Solitary Sclerosis Presenting as Progressive Brainstem Symptoms

A woman in her 30s, presented with left facial weakness, left eyelid droop, left gaze diplopia as well as right facial and upper limb numbness; which progressively worsened over 1 month. She also developed dizziness, dysphonia, dysphagia, and an imbalanced gait. On exam, she had hoarseness, dysarthria, anisocoria; left pupil miosis, left eyelid ptosis, left gaze diplopia, left lower face weakness, deviation of the palate and uvula towards the left side, right eye nystagmus, right sided facial numbness, right upper limb numbness, right dysmetria, brisk reflexes all-over and an unsteady gait. The work up was positive for OCBs in the CSF analysis and MRI brain revealed a single progressive left medulla oblongata and left cerebellar peduncle hyperintensity lesion.

ENDOVASCULAR TREATMENT OF SUBCLAVIAN STEAL SYNDROME: A CLINICAL CASE

The authors presented a clinical case of left subclavian steal syndrome in a 62-year-old man. The main complaints were dizziness, tinnitus, memory loss and unsteady gait. The patient had severe concomitant pathology: coronary heart disease, hypertension, heart failure. X-ray endovascular technologies (balloon dilatation and stenting) made it possible to completely restore blood flow in the affected segment. After treatment, the above complaints disappeared. Minimally invasive X-ray endovascular techniques have particular benefits in patients with severe comorbid pathology.

Ataxic variant of Guillain Barre syndrome: a case report

A 17-year-old girl was admitted after acute onset of unsteady gait succeeding acute gastroenteritis. Neurological examination reported normal power in all four limbs, impaired finger-nose, heel-shin tests, areflexia and ataxic gait. We eliminated other diseases with cerebellar symptoms; for example, Wernicke encephalopathy, multiple sclerosis, cerebellar vascular disease , encephalitis in the brain stem and cerebellum. Blood serum collected from the patient during the acute phase showed no anti-ganglioside antibodies. As the patient presented with evident cerebellar ataxia without muscle weakness, ophthalmoplegia or proprioceptive sensory disruption a diagnosis of ataxic form of Guillain-Barré syndrome (GBS) after nerve conduction studies. Though ataxic GBS is not a settled impression, we should have to give heed to the potential existence of such a scarce GBS variant.

Falls Risk in Long-Term Care Residents With Cognitive Impairment: Effects of COVID-19 Pandemic

ObjectivesThe aim of this study was to investigate the impact of the COVID-19 pandemic on falls rates in long-term care residents with cognitive impairment. DesignAn observational study using routinely collected national interRAI data. Setting and ParticipantsParticipants were from long-term care residents (age ≥60 years) who received an interRAI Long Term Care Facility assessment anywhere in New Zealand between August 17, 2018, and August 16, 2022. MethodsThe primary outcome was “At least 1 fall in the last 30 days.” Based on the Cognitive Performance Scale (CPS), cognitive impairment was categorized into 3 levels: intact or borderline intact (0-1), mild to moderate impairment (2-3), and moderately to very severe impairment (4-6). The COVID-19 pandemic was divided into 3 periods (First wave: March 21, 2020, to June 8, 2020; Varying level of community outbreaks: June 9, 2020 to August 16, 2021; and Delta-Omicron wave: August 17, 2021, to August 16, 2021) and compared to a pre-COVID-19 period (August 17, 2018, to March 20, 2020). Cox regression modeling was used to study falls and interactions between CPS and COVID-19 pandemic periods, along with other established falls risk factors in the literature. ResultsA total of 282,518 interRAI-LTCF assessments from 75,132 unique residents were included. Interactions between CPS and COVID-19 pandemic periods found that cognitive impairment was associated with a higher hazard ratio (ranged from 1.22 to 1.37) in each of the 3 COVID-19 pandemic periods. We also found unstable health, unsteady gait, wandering, and moderate to severe ADL dependency were the strongest risk factors for falls. Conclusions and ImplicationsCognitively impaired long-term care residents had an increased risk for falls during the COVID-19 pandemic. This risk was influenced by several factors. In future pandemic or infection control related isolation, residents who are most at risk can be identified for targeted falls prevention programs.

CAMTA1-related disorder: Phenotypic and molecular characterization of 26 new individuals and literature review.

Calmodulin-binding transcriptional activator 1 (CAMTA1) is highly expressed in the brain and plays a role in cell cycle regulation, cell differentiation, regulation of long-term memory, and initial development, maturation, and survival of cerebellar neurons. The existence of human neurological phenotypes, including cerebellar dysfunction with variable cognitive and behavioral abnormalities (CECBA), associated with CAMTA1 variants, has further supported its role in brain functions. In this study, we phenotypically and molecularly characterize the largest cohort of individuals (n = 26) with 23 novel CAMTA1 variants (frameshift-7, nonsense-6, splicing-1, initiation codon-1, missense-5, and intragenic deletions-3) and compare the findings with all previously reported cases (total = 53). We show that the most notable phenotypic findings are developmental delay/intellectual disability, unsteady or uncoordinated gait, hypotonia, behavioral problems, and eye abnormalities. In addition, there is a high incidence of dysarthria, dysgraphia, microcephaly, gastrointestinal abnormalities, sleep difficulties, and nonspecific brain MRI findings; a few of which have been under-reported. More than one third of the variants in this cohort were inherited from an asymptomatic or mildly affected parent suggesting reduced penetrance and variable expressivity. Our cohort provides a comprehensive characterization of the spectrum of phenotypes and genotypes among individuals with CECBA and the large data will facilitate counseling and formulating management plans and surveillance recommendations for these individuals.

Management of severe congenital femoral deficiency: Does surgical intervention enhance prosthetic function?

The purpose of this study was to evaluate prosthetic outcome in patients with severe congenital femoral deficiency and the potential benefits of surgical intervention on prosthetic fitting and gait. A retrospective review identified 26 active case records with a proximal femoral focal deficiency using a prosthesis. Validated outcome measures evaluated comfort, function, and prosthetic use and quality-of-life assessment. Outcome compared age groups and surgical intervention. Gait analysis performed in 7 patients further evaluated hip and knee function. Eleven male patients and 15 female patients, including 13 children (mean age 10 years, range 5-16) and 13 adults (mean age 36 years, range 23-63) were evaluated. Better prosthetic function and PedsQL scores were recorded in the pediatric group. There was a trend for better scores after surgery. Gait analysis demonstrated reduced hip extension compensated by knee flexion in 3 patients, 2 patients had hip extension with near normal kinematics, 1 untreated patient walked with an unsteady gait, and the remaining walked well using an ischial-bearing prosthesis with pelvic compensatory movements. The management strategy in severe proximal femoral focal deficiency remains a major challenge. Hip reconstruction seems to improve functional scores. Overall, the scores seem to decline into adulthood but not significantly. Gait analysis before further surgical intervention is recommended because compensatory knee flexion may improve step length in terminal stance. Limited numbers, with short follow-up, prevents clear guidance on the benefit of surgery.

Neuropsychiatric disorders associated with recreational nitrous oxide use

Background Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. Purpose This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians’ awareness of this public health problem. Methods We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. Results There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted “V” sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. Conclusion Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.